Aldose Reductase Inhibition

In 1959, the British biochemist Ruth van Heyningen1reported that the cataractous lenses of diabetic rats contain high concentrations of the sugar alcohol sorbitol, which is produced by reduction of the aldehyde group of glucose. Later work by Kinoshita2,3demonstrated that the sorbitol is produced by the action of an enzyme, aldose reductase. Cataractogenesis by sugar alcohols was demonstrated more strikingly in nondiabetic animals fed galactose whose sugar alcohol, galactitol, unlike sorbitol, cannot be further oxidized to a keto sugar by sorbitol dehydrogenase. Hence, galactitol builds to high levels intracellularly faster than sorbitol, producing the same effects, but more rapidly. See also pp 1234 and 1301. Cataracts were the first complication of diabetes to be attributed to the "sorbitol pathway." As more investigators began to explore this pathway, the complexity of the chemical reactions affected by sugar alcohols was found to be greater than anticipated, as was the